Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An enantioselective enzymatic desymmetrization route to hexahydro-4H-furopyranol, a high-affinity ligand for HIV-1 protease inhibitors.

ABSTRACT: An enantioselective synthesis of (3aS,4S,7aR)-hexahydro-4H-furo[2,3-b]pyran-4-ol, a high-affinity nonpeptide ligand for a variety of potent HIV-1 protease inhibitors is described. The key steps involved a highly enantioselective enzymatic desymmetrization of meso-diacetate, an efficient transacetalization, and a highly diastereoselective reduction of a ketone. This route is amenable to large-scale synthesis using readily available starting materials.

SUBMITTER: Ghosh AK

PROVIDER: S-EPMC5708567 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

An enantioselective enzymatic desymmetrization route to hexahydro-4H-furopyranol, a high-affinity ligand for HIV-1 protease inhibitors.

Ghosh Arun K AK Sarkar Anindya A

Tetrahedron letters 20170703 33

An enantioselective synthesis of (3aS,4S,7aR)-hexahydro-4H-furo[2,3-b]pyran-4-ol, a high-affinity nonpeptide ligand for a variety of potent HIV-1 protease inhibitors is described. The key steps involved a highly enantioselective enzymatic desymmetrization of meso-diacetate, an efficient transacetalization, and a highly diastereoselective reduction of a ketone. This route is amenable to large-scale synthesis using readily available starting ...[more]

PMID: 29200514

Similar Datasets

A Photochemical Route to Optically Active Hexahydro-4H-furopyranol, a High-Affinity P2 Ligand for HIV-1 Protease Inhibitors.

Project description:We describe here the syntheses of optically pure (3aS,4S,7aR)-hexahydro-4H-furo[2,3-b]pyran-4-ol and (3aR,4R,7aS)-hexahydro-4H-furo[2,3-b]pyran-4-ol. These stereochemically defined heterocycles are important high-affinity P2 ligands for a variety of highly potent HIV-1 protease inhibitors. The key steps involve an efficient Paternò-Büchi [2 + 2] photocycloaddition, catalytic hydrogenation, acid-catalyzed cyclization to form the racemic ligand alcohol, and an enzymatic resolution with immobilized Amano Lipase PS-30. Optically active ligands (-)-6 and (+)-6 were obtained with high enantiomeric purity. Enantiomer (-)-6 has been converted to potent HIV-1 protease inhibitor 3.

| S-EPMC7048240 | biostudies-literature

Enantioselective Syntheses of (-)-Alloyohimbane and (-)-Yohimbane by an Efficient Enzymatic Desymmetrization Process.

Project description:Enantioselective syntheses of (-)-alloyohimbane and (-)-yohimbane was accomplished in a convergent manner. The key step involved a modified mild protocol for the enantioselective enzymatic desymmetrization of meso-diacetate. The protocol provided convenient access to an optically active monoacetate in multi-gram scale in high enantiomeric purity. This monoacetate was converted to (-)-alloyohimbane. Reductive amination of the derived aldehyde causes the isomerization leading to the trans-product and allows the synthesis of (-)-yohimbane.

| S-EPMC5526648 | biostudies-literature

Scaffolding catalysts: highly enantioselective desymmetrization reactions.

Project description:Ex-changing places: a highly enantioselective desymmetrization of 1,2-diols has been developed in which the catalyst utilizes reversible covalent bonding to the substrate to achieve both high selectivity and rate acceleration (see scheme, PMP=pentalmethylpiperidine, TBS=tert-butyldimethylsilyl). Induced intramolecularity is responsible for the enhanced rate, thus allowing the reaction to be performed at room temperature.

| S-EPMC3366164 | biostudies-literature

Efficient, enantioselective assembly of silanediol protease inhibitors.

Project description:A five-step assembly of silicon-protected dipeptide mimics from commercially available reagents is described. This methodology makes silanediol protease inhibitors readily available for the first time. The sequence features asymmetric hydrosilylation, a novel reduction of a silyl ether to a silyllithium reagent, and addition of this dianion to a sulfinimine, to produce the complete inhibitor skeleton with full control of stereochemistry. Oxidation of the primary alcohol to an acid completes the synthesis.

| S-EPMC3064730 | biostudies-literature

AcsD catalyzes enantioselective citrate desymmetrization in siderophore biosynthesis.

Project description:Bacterial pathogens need to scavenge iron from their host for growth and proliferation during infection. They have evolved several strategies to do this, one being the biosynthesis and excretion of small, high-affinity iron chelators known as siderophores. The biosynthesis of siderophores is an important area of study, not only for potential therapeutic intervention but also to illuminate new enzyme chemistries. Two general pathways for siderophore biosynthesis exist: the well-characterized nonribosomal peptide synthetase (NRPS)-dependent pathway and the NRPS-independent siderophore (NIS) pathway, which relies on a different family of sparsely investigated synthetases. Here we report structural and biochemical studies of AcsD from Pectobacterium (formerly Erwinia) chrysanthemi, an NIS synthetase involved in achromobactin biosynthesis. The structures of ATP and citrate complexes provide a mechanistic rationale for stereospecific formation of an enzyme-bound (3R)-citryladenylate, which reacts with L-serine to form a likely achromobactin precursor. AcsD is a unique acyladenylate-forming enzyme with a new fold and chemical catalysis strategy.

| S-EPMC2644304 | biostudies-literature

Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones.

Project description:The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles via an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual catalytic system, that provides synchronous activation of the cyclohexanone with a chiral prolinamide and the allene with a copper(i) co-catalyst to deliver the stereodefined bicyclic core, is described. Successful application to oxygen analogues was also achieved, thereby providing a new enantioselective synthetic entry to architecturally complex bicyclic ethereal frameworks. The mechanistic pathway and the origin of enantio- and diastereoselectivities has been uncovered using density functional theory (DFT) calculations.

| S-EPMC8159440 | biostudies-literature

Enantioselective Desymmetrization of Methylenedianilines via Enzyme-Catalyzed Remote Halogenation.

Project description:Extensive effort has been devoted to engineering flavin-dependent halogenases (FDHs) with improved stability, expanded substrate scope, and altered regioselectivity. Here, we show that variants of rebeccamycin halogenase (RebH) catalyze enantioselective desymmetrization of methylenedianilines via halogenation of these substrates distal to their pro-stereogenic center. Structure-guided engineering was used to increase the conversion and selectivity of these reactions, and the synthetic utility of the halogenated products was shown via conversion of to a chiral α-substituted indole. These results constitute the first reported examples of asymmetric catalysis by FDHs.

| S-EPMC5898188 | biostudies-literature

Mechanistically Inspired Route toward Hexahydro-2H-chromenes via Consecutive [4 + 2] Cycloadditions.

Project description:Utilizing two robust C-C bond-forming reactions, the Baylis-Hillman reaction and the Diels-Alder reaction, we report a highly enantio-, regio-, and diastereoselective synthesis of hexahydro-2H-chromenes via two sequential [4 + 2] cycloadditions. These tandem and formal cycloadditions have also been performed as a "one-pot" sequence to access the corresponding heterocycles constituting up to five contiguous stereocenters in excellent yields and stereoselectivity.

| S-EPMC5342895 | biostudies-literature

Dual Nickel- and Photoredox-Catalyzed Enantioselective Desymmetrization of Cyclic meso-Anhydrides.

Project description:The enantioselective desymmetrization of cyclic meso-anhydrides with benzyl trifluoroborates under nickel-photoredox catalysis is described. The reaction tolerates a variety of sterically and electronically different trifluoroborates, as well as structurally unique cyclic anhydrides. The trans isomer of the keto-acid products is also observed at varying levels dependent on the trifluoroborate identity and relative catalyst loading. A mechanism involving decarbonylation and Ni-C bond homolysis of a NiII adduct is proposed. This feature allows access to a trans keto-acid as the major product in high enantioselectivity from a cis meso anhydride.

| S-EPMC5510164 | biostudies-literature

Palladium-Catalyzed, Enantioselective Desymmetrization of N-Acylaziridines with Indoles.

Project description:Ring opening reactions of meso-aziridines generate chiral amine derivatives where the control of stereochemistry is possible through enantioselective catalysis. We report the use of a diphosphine-palladium(II) catalyst for the highly enantioselective desymmetrization of N-acylaziridines with indoles. The β-tryptamine products are isolated in moderate to high yield across a range of indole and aziridine substitution patterns. The synthetic utility of β-tryptamine products is demonstrated by conversion to the brominated pyrroloindoline derivative.

| S-EPMC9022218 | biostudies-literature